2,285 research outputs found
miRNA profiles as a predictor of chemoresponsiveness in Wilms' tumor blastema.
The current SIOP treatment protocol for Wilms' tumor involves pre-operative chemotherapy followed by nephrectomy. Not all patients benefit equally from such chemotherapy. The aim of this study was to generate a miRNA profile of chemo resistant blastemal cells in high risk Wilms' tumors which might serve as predictive markers of therapeutic response at the pre-treatment biopsy stage. We have shown here that unsupervised hierarchical clustering of genome-wide miRNA expression profiles can clearly separate intermediate risk tumors from high risk tumors. A total of 29 miRNAs were significantly differentially expressed between post-treatment intermediate risk and high risk groups, including miRNAs that have been previously linked to chemo resistance in other cancer types. Furthermore, 7 of these 29 miRNAs were already at the pre-treatment biopsy stage differentially expressed between cases ultimately deemed intermediate risk compared to high risk. These miRNA alterations include down-regulation in high risk cases of miR-193a.5p, miR-27a and the up-regulation of miR-483.5p, miR-628.5p, miR-590.5p, miR-302a and miR-367. The demonstration of such miRNA markers at the pre-treatment biopsy stage could permit stratification of patients to more tailored treatment regimens
Fair scans of the seesaw. Consequences for predictions on LFV processes
Usual analyses based on scans of the seesaw parameter-space can be biassed
since they do not cover in a fair way the complete parameter-space. More
precisely, we show that in the common "R-parametrization", many acceptable
R-matrices, compatible with the perturbativity of Yukawa couplings, are
normally disregarded from the beginning, which produces biasses in the results.
We give a straightforward procedure to scan the space of complex R-matrices in
a complete way, giving a very simple rule to incorporate the perturbativity
requirement as a condition for the entries of the R-matrix, something not
considered before. As a relevant application of this, we show that the extended
believe that BR(mu --> e, gamma) in supersymmetric seesaw models depends
strongly on the value of theta_13 is an "optical effect" produced by such
biassed scans, and does not hold after a careful analytical and numerical
study. When the complete scan is done, BR(mu --> e, gamma) gets very
insensitive to theta_13. Moreover, the values of the branching ratio are
typically larger than those quoted in the literature, due to the large number
of acceptable points in the parameter-space which were not considered before.
Including (unflavoured) leptogenesis does not introduce any further dependence
on theta_13, although decreases the typical value of BR(mu --> e, gamma).Comment: 22 pages, 5 figure
Positive words carry less information than negative words
We show that the frequency of word use is not only determined by the word
length \cite{Zipf1935} and the average information content
\cite{Piantadosi2011}, but also by its emotional content. We have analyzed
three established lexica of affective word usage in English, German, and
Spanish, to verify that these lexica have a neutral, unbiased, emotional
content. Taking into account the frequency of word usage, we find that words
with a positive emotional content are more frequently used. This lends support
to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias
in human expression. We also find that negative words contain more information
than positive words, as the informativeness of a word increases uniformly with
its valence decrease. Our findings support earlier conjectures about (i) the
relation between word frequency and information content, and (ii) the impact of
positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table
The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.
The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations
Classical skyrmions in SU(N)/SO(N) cosets
We construct the skyrmion solutions appearing in the coset spaces SU(N)/SO(N)
for N > 2 and compute their classical mass. For N = 3, the third homotopy group
pi_3(SU(3)/SO(3)) = Z_4 implies the existence of two distinct solutions: the
skyrmion of winding number two has spherical symmetry and is found to be the
lightest non-trivial field configuration; the skyrmion and antiskyrmion of
winding number plus and minus one are slightly heavier and of toroidal shape.
For N >= 4, there is only one skyrmion since the third homotopy group is Z_2.
It is found to have spherical symmetry and is significantly lighter than the N
= 3 solutions.Comment: 14 pages, 3 figures; v2: discussion improve
The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat
We describe the SPIDER flight cryostat, which is designed to cool six
millimeter-wavelength telescopes during an Antarctic long-duration balloon
flight. The cryostat, one of the largest to have flown on a stratospheric
payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6
K. Stainless steel capillaries facilitate a high flow impedance connection
between the main liquid helium tank and a smaller superfluid tank, allowing the
latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank.
Each telescope houses a closed cycle helium-3 adsorption refrigerator that
further cools the focal planes down to 300 mK. Liquid helium vapor from the
main tank is routed through heat exchangers that cool radiation shields,
providing negative thermal feedback. The system performed successfully during a
17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold
time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig
An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.
ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly
Economics methods in Cochrane systematic reviews of health promotion and public health related interventions.
Peer reviewedPublisher PD
Dangerous Skyrmions in Little Higgs Models
Skyrmions are present in many models of electroweak symmetry breaking where
the Higgs is a pseudo-Goldstone boson of some strongly interacting sector. They
are stable, composite objects whose mass lies in the range 10-100 TeV and can
be naturally abundant in the universe due to their small annihilation
cross-section. They represent therefore good dark matter candidates. We show
however in this work that the lightest skyrmion states are electrically charged
in most of the popular little Higgs models, and hence should have been directly
or indirectly observed in nature already. The charge of the skyrmion under the
electroweak gauge group is computed in a model-independent way and is related
to the presence of anomalies in the underlying theory via the
Wess-Zumino-Witten term.Comment: 31 pages, 4 figures; v2: minor changes, one reference added, version
to appear in JHEP; v3: erratum added, conclusions unchange
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